In a large-scale prospective cohort study, researchers identified two frequently consumed food additive mixtures that may be associated with an elevated risk of type 2 diabetes, independent of the nutritional quality of the diet.
The study, conducted within the French NutriNet-Santé cohort, followed 108,643 participants over a mean period of 7.7 years and identified 1,131 incident cases of type 2 diabetes. Using nonnegative matrix factorization, researchers identified five common food additive mixtures in participants' diets, two of which were positively associated with type 2 diabetes incidence, researchers reported in PLOS Medicine.
The first mixture (mixture 2) primarily contained emulsifiers, preservatives, and a dye: modified starches, pectin, guar gum, carrageenan, polyphosphates, potassium sorbates, curcumin, and xanthan gum. This mixture was associated with an increased risk of type 2 diabetes (hazard ratio [HR] = 1.08) per 1–standard deviation increment in exposure. The second mixture (mixture 5) was composed of citric acid, sodium citrates, phosphoric acid, sulphite ammonia caramel, acesulfame K, aspartame, sucralose, arabic gum, malic acid, carnauba wax, paprika extract, anthocyanins, guar gum, and pectin, and was associated with a higher risk of type 2 diabetes (HR = 1.13).
This study addressed a gap in prior research that evaluated additives individually. “To our knowledge, this study is the first to estimate the exposure to food additive mixtures in a large population-based cohort and investigate their link with type 2 diabetes incidence,” researchers noted.
Exploratory analyses revealed both synergistic and antagonistic interactions between various food additives within these mixtures. For mixture 2, three synergistic and four antagonistic interactions were identified among the eight most characteristic additives. For mixture 5, which included 14 key additives, 6 synergistic and 4 antagonistic interactions were found.
Mixture 2 was most strongly associated with consumption of broths, dairy desserts, and fats and sauces; mixture 5 was correlated with artificially sweetened beverages.
The researchers adjusted for a wide range of potential confounding factors, including age, sex, body mass index, physical activity level, smoking status, educational level, socioprofessional category, monthly household income, family history of type 2 diabetes, and numerous dietary variables such as energy intake, saturated fat, sodium, fiber, alcohol, and added sugars. The associations remained robust across multiple sensitivity analyses.
The authors additionally performed mediation analyses. Mixture 5 was found to mediate 42% of the association between sugary drinks and type 2 diabetes and 52% of the association with artificially sweetened beverages. Mixture 2 mediated 18% of the association between fats and sauces and diabetes.
The researchers also confirmed that the additive mixtures were stable across two follow-up periods (2009 to 2016 and 2017 to 2024), further supporting the robustness of the findings.
“These results suggest that food additives found in a wide variety of products and frequently consumed together may potentially represent a modifiable risk factor for type 2 diabetes prevention,” the authors concluded. “They support public health recommendations to limit nonessential additives.”
The researchers acknowledged several limitations of the study, including potential exposure misclassification, residual confounding, and the inability to infer causality from this observational study. They noted the need for further experimental research to elucidate underlying mechanisms, particularly with regard to synergistic and antagonistic effects between food additives.
The authors declared no competing interests.